BRIEF REPORT Atezolizumab-Induced Aseptic Meningitis in Patients with NSCLC Ryo Toyozawa, MD, a Naoki Haratake, MD, PhD, a Gouji Toyokawa, MD, PhD, b Taichi Matsubara, MD, PhD, a Shinkichi Takamori, MD, PhD, a Naoko Miura, MD, PhD, a Masafumi Yamaguchi, MD, PhD, a Mitsuhiro Takenoyama, MD, PhD, a Takashi Seto, MD, PhD a, * a Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan b Department of Thoracic Surgery, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan Received 30 January 2020; revised 31 January 2020; accepted 2 February 2020 Available online - 13 February 2020 ABSTRACT Introduction: During treatment with immune checkpoint inhibitors, immune-related adverse events sometimes occur, and their management is a critical concern asso- ciated with such treatment. Encephalitis and meningitis are some of the critical immune-related adverse events. Atezolizumab is an immune checkpoint inhibitor that inhibits the programmed cell death-ligand. Encephalitis and meningitis were reported in 0.8% of the patients in the atezolizumab versus docetaxel in patients with pre- viously treated NSCLC. However, none of the reports have clarified the details concerning atezolizumab- induced encephalitis and meningitis, including their background, time of onset, treatment, and therapeutic course. We herein report about three patients who experienced atezolizumab-induced meningitis in our department. Methods: Of the 29 patients who received atezolizumab in our department between October 2015 and September 2018, three developed aseptic meningitis. We retrospec- tively examined their clinical, radiologic, and cytologic features. Results: In all three cases, a depressed level of conscious- ness followed fever in cycle 1, days 15 and 16 after administration of atezolizumab. Cerebrospinal fluid exami- nation revealed that the number of cells was not increased despite the protein level being high. No definite malignant cells were identified in the cerebrospinal fluid in any of the three cases. Only one patient exhibited abnormal enhance- ment along the lines of the corpus callosum on magnetic resonance imaging. On the basis of these findings, the patients were diagnosed with atezolizumab-induced men- ingitis. After the administration of methylprednisolone (1000 mg for 3 d), they promptly became conscious and alert. *Corresponding author. Disclosure: Dr. Toyozawa reports receiving personal fees from Astra- Zeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan, Kyowa Hakka Kirin, MSD, Nippon Boehringer lngelheim, Nippon Kayaku, Novartis Pharma, Ono Pharmaceutical, and Tai ho Pharmaceutical and grants from Abbvie, Daiichi Sankyo, Pfizer Japan, and Takeda Pharmaceutical outside of the submitted work. Dr. Haratake reports receiving personal fees from Bristol-Myers Squibb, Chugai Pharmaceutical, and MSD outside of the submitted work. Dr. Takamori reports receiving personal fees from AstraZeneca and Chugai Pharmaceutical outside of the submitted work. Dr. Miura reports receiving personal fees from Nippon Boehringer lngelheim, Ono Pharmaceutical, and Tai ho Pharmaceutical outside of the submitted work. Dr. Yamaguchi reports receiving grants and personal fees from Chugai Pharmaceutical; personal fees from AstraZeneca, Covidien Japan, Daiichi Sankyo, Eli Lilly Japan, Kyowa Hakko Kirin, Nippon Boehringer lngelheim, Ono Pharmaceutical, and Tai ho Pharmaceutical; and grants from Pfizer Japan outside of the submitted work. Dr. Takenoyama reports receiving grants and personal fees from AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Covidien Japan, Eli Lilly Japan, Johnson & Johnson, Kyowa Hakko Kirin, MSD, Nippon Boehringer lngelheim, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, and Tai ho Pharmaceutical; personal fees from Nippon Kayaku; and grants from KM Biologics outside of the submitted work. Dr. Seto reports receiving grants and personal fees from AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, MSD, Nippon Boehringer lngelheim, Novartis Pharma, Pfizer Japan, Takeda Pharmaceutical; personal fees from Astellas Pharma, Bristol-Myers Squibb, Kyowa Hakko Kirin, Ono Pharmaceutical, Taiho Pharmaceutical, and Thermo Fisher Scientific; and grants from Abbvie, Sayer Yakuhin, Kissei Pharmaceutical, LOXO Oncology, and Merck Serono outside of the submitted work. The remaining authors declare no conflict of interest. Address for correspondence: Takashi Seto, MD, PhD, Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka 811-1395, Japan. E-mail: [email protected] Cite this article as: Toyozawa R, et al. Atezolizumab-Induced Aseptic Meningitis in Patients with NSCLC. JTO Clin Res Rep 1:100012 ª 2020 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). ISSN: 2666-3643 https://doi.org/10.1016/j.jtocrr.2020.100012 JTO Clinical and Research Reports Vol. 1 No. 1: 1-4
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